The polyol 1,5-anhydroglucitol (AG) present in human plasma is derived largely from ingestion and is excreted un-metabolized. A variety of polyols also accumulate in tissues of diabetes, and their concentrations can be measured by isotope dilution mass spectrometry. Reduction of plasma (AG) has been noted in diabetics and is due to accelerated excretion of AG during hyperglycemia. Plasma [AG] has therefore been proposed as a marker for glycemic control. A precise understanding of its utility relies on a quantitative understanding of the mass balance for AG. In this study, non-steady-state data were analyzed to develop a dynamic mass balance model for AG that is based on a two-compartment model. The data was consistent with a model in which exchange between tissue and plasma pools is rapid and in which the tissue compartment mass is two to three times the mass of the plasma compartment. According to model estimates, accelerated excretion of AG due to hyperglycemia can c ause marked net depletion of total AG over a time scale of days. Recovery from a depleted state is slow because the total body capacity represents >5 wk of normal intake. Accordingly, AG monitoring should be able to indicate the presence of past glucosuric hyperglycemic episodes during a period of days to weeks, as well as provide information on the extent to which high deviations from the average plasma glucose concentration are operative.